Impaired glucose tolerance in pancreas grafted diabetic patients is due to insulin secretory defects.

INTRODUCTION: Pancreas transplantation in diabetic patients can sustain insulin independence for years. The aim of the study was to measure the incidence of an impaired or diabetic glucose tolerance in patients after successful transplantation and analyse insulin resistance and insulin secretion. METHODS: 174 Type 1 diabetic recipients of simultaneous pancreas/kidney (SPK) transplants were investigated early (three months) and 95 patients late (five years) after transplantation using an oral glucose tolerance test combined with an iv arginine load. RESULTS: Although mean fasting blood glucose and HbA1c levels were within the normal range, only 65% of the patients displayed a normal glucose tolerance (NGT), whereas 25% had an impaired (IGT) and 10% showed a diabetic glucose tolerance (DGT). Fasting blood glucose and HbA1c values were significantly lower in patients with NGT compared to graft recipients with IGT or DGT, either three months or five years after SPK. Indicators of insulin resistance (fasting insulin, HOMA-IR, Matsuda/de Fronzo Index) were elevated in all graft recipients, but no differences were found between groups. In contrast insulin secretion was significantly reduced in patients with IGT and DGT early and late after transplantation. SUMMARY: Insulin resistance is a common feature after pancreas transplantation. However, either three months or five years after SPK abnormal glucose tolerance was mainly due to a reduced glucose- and arginine-induced secretory response of insulin.     

Establishment of a pig model with enteric and portal venous drainage of pancreatoduodenal transplantation

AIM: To establish the pig model of pancreatoduodenal transplantation with enteric drainage (ED) and portal venous drainage (PVD). METHODS: Forty-six hybrid Landrace pigs were divided into two groups (donors and recipients) randomly, and pancreatoduodenal allotransplantation was performed. Donors were perfused via abdominal aorta without clamping the portal venous outflow with UW solution at 80-100 cm H_2O after heparinization. Whole pancreatoduodenal grafts were harvested with segments of abdominal aorta and portal vein, and shaped under 4℃ UW solution. Then, end-to-end anastomosis was performed with the donor iliac artery bifurcation Y graft to the recipient superior mesenteric artery and celiac artery. Furthermore, type I diabetes model was made by removal of the recipient pancreas. The venous anastomosis was reconstructed between the donor portal vein and the recipient superior mesentery vein. Meanwhile, end-toside anastomosis was performed with the donor common iliac artery bifurcation Y graft to the recipient abdominal aorta, and side-to-side intestinal anastomosis was performed between the donor duodenum and the recipient jejunum. External jugular vein was intubated for transfusion. Levels of plasma glucose, insulin and glucagon were measured during the operation and on the 1~(st), 3~(rd), 5~(th), and 7~(th) d after operation. RESULTS: Pancreatoduodenal allotransplantation was performed on 23 pigs of which 1 died of complication of anesthesia. The success rate of operation was 95.6%. Complications of operation occurred in two cases in which one was phlebothrombosis with an incidence of 4.6%, and the other was duodenojejunal anastomotic leak with an incidence of 4.6%. The level of plasma glucose decreased within 30 min, after removal of pancreas and recovered on the 2~(nd) d after operation. The level of plasma insulin and glucagon increased within 30 min after removal of pancreas and recovered on the 2~(nd) d after operation. Rejection occurred on the 1~(st) d and reached the worst level on the 7~(th) d after transplantation, without change of plasma insulin and glucagon or clinical symptoms of rejection. CONCLUSION: Pancreatoduodenal transplantation in pigs can treat type I diabetes. ED and PVD can keep the function of endocrine in normal. The technique of pancreatoduodenal transplantation with ED and PVD may pave the way for the further application of pancreas transplantation in clinic.     

门静脉回流技术在胰肾联合移植动物实验中的应用

目的研究门静脉回流技术在胰肾联合移植动物实验中的应用。方法 24只杂交长白猪随机分为体循环回流组(SVD)和门静脉回流组(PVD),每组内随机分为供、受体,经供体猪腹主动脉原位灌注,大块联合切取供体胰、节段十二指肠、左肾、脾脏。修剪移植肾脏、胰腺和十二指肠,左肾静脉与肠系膜上静脉吻合后．PVD组采用移植物门静脉与受体肠系膜上静脉吻合,SVD组采用移植物门静脉与下腔静脉吻合。各组腹主动脉与受体腹主动脉吻合,十二指肠内置人T型管、输尿管内置人脑室引流管自腹壁引出待Ⅱ期手术吻合。结果 SVD组和PVD组手术均很成功,供肾、胰植入受体后立即恢复良好的血液循环,并且迅速恢复功能,平均存活期分别为12d和14d。结论门静脉回流技术是可行的。     

Metabolic follow-up after long-term pancreas graft survival

DESIGN: Successful pancreas transplantation results in insulin independence and normoglycemia. This prospective study was performed to investigate long-term metabolic changes after pancreas transplantation. METHODS: Thirty-eight type 1 diabetic patients after simultaneous pancreas/kidney transplantation (SPK) with a pancreas graft survival for at least 10 years were studied in a prospective manner. HbA(1c) and glucose levels before and during an oral glucose tolerance test (OGTT) were analyzed from 3 months to 10 years after SPK. In addition, insulin secretion and glucagon response were measured. RESULTS: Fasting glucose increased slightly and continuously from 3 months to 10 years (from 78 +/- 3 to 91 +/- 2 mg/dl). Even HbA(1c) levels showed a mild but significant increase from 3 months to 10 years after SPK. Glucose tolerance deteriorated markedly 10 years after SPK. Insulin secretion during OGTT remained stable for 10 years. Parameters of insulin resistance and sensitivity did not change significantly but glucagon secretion increased significantly during the course after SPK. Late after SPK, glucagon levels were higher in patients with an impaired or diabetic glucose tolerance. CONCLUSIONS: Pancreas transplantation is able to restore endogenous insulin secretion for 10 years or more. Especially, late after SPK, a deterioration of glycemic control was detected, even if glucose values were within the normal range. During prospective long-term follow-up, an increase of glucagon secretion but no decrease of insulin secretion was detected.     

Comparison of pancreas-transplanted type 1 diabetic patients with portal-venous versus systemic-venous graft drainage: impact on glucose regulatory hormones and the growth hormone/insulin-like growth factor-I axis

CONTEXT: Pancreas grafts can be drained through the iliac vein (systemic drainage) or the portal vein. OBJECTIVE: We hypothesized that normalization of portal insulin in patients with portal pancreas graft drainage stimulates the GH/IGF-I axis and thereby contributes to glucose control. METHODS: We compared patients after combined kidney and pancreas transplantation with portal drainage (n = 7) to patients with systemic drainage of the pancreas graft (n = 8) and nondiabetic controls (n = 8). Overnight fasting sera were analyzed for free and total IGF-I and IGF-binding proteins. Glucose regulatory hormones were examined after an oral glucose tolerance test and GH after stimulation with GHRH. RESULTS: Systemic drainage led to higher basal and stimulated insulin levels than portal drainage (P < 0.05), but increments in response to oral glucose were reduced in both transplanted groups (P < 0.05 vs. controls). However, glucose tolerance was similar in all groups. Circulating free and total IGF-I and IGF-binding protein-3 were similar to control levels in the systemic drainage group but elevated in the portal drainage group (P < 0.05). Consistently, the GH response was reduced in the portal drainage group (P < 0.05 vs. controls) and correlated inversely with free IGF-I (r = -0.63, P < 0.05). CONCLUSION: Portal drainage of pancreatic endocrine secretion in pancreas graft recipients raises IGF-I and lowers GH secretion. These changes might explain that glucose regulation is maintained despite lower peripheral insulin levels, compared with patients with systemic graft drainage and nondiabetic control subjects.     

Effect of venous drainage site on insulin action after pancreas transplantation in the rat--is there insulin resistance and a risk for atherosclerosis?

The aim of the present study was to determine the influence of the venous drainage site on insulin homeostasis and the possible risk for atherosclerosis development after pancreas transplantation. We studied inbred rats that received pancreas transplants with either systemic (STX) or portal (PTX) venous drainage after prior induction of diabetes with streptozotocin and sham-operated controls. The observation period was 6 months. Fasting plasma glucose and insulin levels were similar in all 3 groups, but fasting plasma glucagon levels were elevated in STX (mean +/- SEM, 282+/-35 ng/L) in comparison to PTX rats (119+/-9 ng/L, P < .05), although the difference versus the control group (191+/-31 ng/L) was insignificant. Glucose utilization and hepatic glucose production (HGP), assessed by a dose-response euglycemic-hyperinsulinemic clamp in combination with tritiated glucose infusion, were similar in all 3 groups. The groups were also similar with respect to the molar ratio of plasma C-peptide and insulin during basal steady state and the metabolic clearance rate (MCR) of insulin during the clamp studies, suggesting an unchanged hepatic insulin extraction (HIE) after transplantation with either technique. Factors known to be related to atherosclerosis, ie, blood pressure, intracellular magnesium, and fasting levels of plasma cholesterol, triglycerides, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, were similar in all 3 groups. Light microscopy of the aorta showed a slightly thicker intima in STX rats (24.3+/-0.5 microm, P < .05) versus PTX rats (21.4+/-0.7 microm) and control (21.4+/-0.6 microm); however, atherosclerosis-like lesions were absent in all 3 groups. In conclusion, in a rat model with streptozotocin-diabetes and pancreas transplantation but no need for immunosuppression, both systemic and portal venous drainage avoid peripheral and hepatic insulin resistance; also, there is no increased risk for atherosclerosis.     

Sequential metabolic studies of pancreas allograft function in type 1 diabetic recipients.

We have previously shown that the loss of acute first phase insulin secretion precedes pancreas allograft rejection and development of glucose intolerance in Type 1 diabetic patients. In order to examine whether there is a progressive loss of phases of insulin secretion and beta-cell function in technically successful pancreas transplants during the first year, we measured glucose, insulin, and C-peptide responses to physiological (mixed meal) and pharmacological (IV glucose and IV glucagon) stimulation in 27 glucose-tolerant, insulin-independent allograft recipients at 3, 6, and 12 months. Mean +/- SE fasting serum glucose levels were normalized throughout the study period. Postprandial serum glucose profiles tended to increase by 12 months compared to 3 and 6 months, although peak glucose levels were not statistically different. Following pancreas transplantation, basal serum insulin levels were high at 3 months (163 +/- 17 pM), 6 months (165 +/- 22 pM), and 12 months (248 +/- 54 pM, p = NS) in the Type 1 diabetic pancreas allograft recipients when compared to normal (25 +/- 3 pM). We observed slight elevations in postprandial insulin and C-peptide profiles at 12 months compared to 3 and 6 months. Following IV glucose and glucagon stimulation, serum insulin and C-peptide levels as well as phases of insulin release did not differ over the 12-month study period. Similarly, the glucose decay constant (KG) was nearly identical at 3, 6, and 12 months. In summary, 1 year following successful whole cadaveric, heterotopic pancreas transplantation in Type 1 diabetic recipients, fasting serum glucose remains normalized, while postprandial glucose tends to rise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Post-transplantation hypoglycaemia in type 1 diabetic pancreas allograft recipients

Physiologic replacement of insulin in patients with type 1 (insulin-dependent) diabetes following pancreas allograft transplantation results in normoglycaemia during fasting and postprandial states. However, this is achieved at the expense of peripheral hyperinsulinaemia in the heterotopic pancreas allograft recipients with systemic insulin drainage. In addition, the pancreas allograft is denervated and thus devoid of autonomic nervous regulation of pancreatic beta-cell secretion. Recent reports of hypoglycaemia (symptomatic and asymptomatic), which can be fatal, have raised serious concerns regarding the aetiology of the hypoglycaemic epiphenomon in type 1 diabetic pancreas allograft recipients. Although the prevalence of significant hypoglycaemia following pancreas transplantation remains unknown, it is important to conduct studies to determine the mechanisms, the natural history, predictors and treatment as well as the long-term prognosis (graft and patient survival rates) of type 1 diabetic patients who develop pancreas-allograft-associated hypoglycaemia. Indeed, predictors of hypoglycaemia following pancreas allograft could significantly impact on the selection of appropriate therapeutic options for pancreas allograft transplantation. Finally, whether postpancreas allograft transplantation-associated hypoglycaemia in type 1 diabetic patients carries greater morbidity and mortality when compared to those without hypoglycaemia deserves to be investigated Received: 8 September 1998 / Accepted in revised form: 14 September 1998     

Peripheral insulin release after pancreatic resection: the effect of decreased beta-cell mass with systemic or portal drainage

Surgical alteration of the pancreas can result in several anatomic alterations which may affect insulin release. We evaluated the effects of resection, systemic drainage, and autotransplantation of the canine pancreas on peripheral insulin levels and glucose disposal as measured by iv glucose tolerance tests (IVGTT) and a steady state hyperglycemic challenge (clamp). Proximal pancreatectomy (PPx) with reduced beta-cell mass and intact portal drainage resulted in a modestly elevated fasting glucose level and increased integrated glucose response to IVGTT. Compared to preoperative normals, basal insulin was unchanged from preoperative controls; however, peak insulin and integrated insulin response to IVGTT were decreased in PPx animals. Splenocaval drainage or autotransplantation of the distal pancreas resulted in normalization of the severely altered insulin response and fasting glucose levels. K values were significantly reduced after all three procedures. Clamp studies confirmed the basal glucose and insulin findings of the IVGTT. During the clamp, PPx animals had peripheral insulin values approximately 50% of normal controls, while autotransplantation and splenocaval drainage animals had insulin values that approximate normal controls. All three postsurgical groups had blunted insulin levels during stable hyperglycemia. Glucose utilization rates were severely decreased in all three groups. Reduction of beta-cell mass with intact portal drainage resulted in reduced insulin response to glucose challenge by either IVGTT or clamp. Systemic drainage of this same reduced beta-cell mass resulted in peripheral insulin levels comparable to normal controls. Denervation (autotransplantation) had little additive effect. All three groups demonstrated severely decreased rates of glucose disappearance as measured by both IVGTT and clamp studies. Therefore, reduction in beta-cell mass, drained systemically or portally, results in altered glucose disposal regardless of the peripheral insulin levels.     

Consequences of systemic venous drainage and denervation of heterotopic pancreatic transplants for insulin/C-peptide profiles in the basal state and after oral glucose

Plasma glucose, immunoreactive insulin and C-peptide concentrations were compared in nine pancreas-kidney-transplanted patients (systemic venous drainage) and in ten non-diabetic kidney-transplanted patients with similar kidney function. In the basal state, C-peptide (insulin secretion) was similar, but immunoreactive insulin was higher and glucose concentrations were slightly, but significantly lower in pancreas-transplanted patients. After 50 g oral glucose, the plasma glucose and IR-insulin profiles were similar in both groups. The circumvention of first-pass hepatic insulin extraction (decreased endogenous insulin clearance) was compensated for by a significant reduction in insulin secretion (C-peptide; p=0.036). In conclusion, hyperinsulinaemia in pancreas-transplanted patients with systemic venous drainage is significant only in the basal state. Insulin delivered into the portal and peripheral circulation, when leading to similar insulin profiles, maintains comparable degrees of glucose tolerance.     

Results of pancreas transplantation alone with special attention to native kidney function and proteinuria in type 1 diabetes patients

We report on our single-center experience with pancreas transplantation alone (PTA) in 71 patients with type 1 diabetes, and a 4-year follow-up. Portal insulin delivery was used in 73.2% of cases and enteric drainage of exocrine secretion in 100%. Immunosuppression consisted of basiliximab (76%), or thymoglobulin (24%), followed by mycophenolate mofetil, tacrolimus, and low-dose steroids. Actuarial patient and pancreas survival at 4 years were 98.4% and 76.7%, respectively. Relaparatomy was needed in 18.3% of patients. Restored endogenous insulin secretion resulted in sustained normalization of fasting plasma glucose levels and HbA1c concentration in all technically successful transplantations. Protenuria (24-hour) improved significantly after PTA. Renal function declined only in recipients with pretransplant glomerular filtration rate (GFR) greater than 90 ml/min, possibly as a result of correction of hyperfiltration following normalization of glucose metabolism. Further improvements were recorded in several cardiovascular risk factors, retinopathy, and neuropathy. We conclude that PTA was an effective and reasonably safe procedure in this single-center experience.     

Indikation und Ergebnisse der simultanen Nieren-Pankreas-Transplantation

In Germany approximately 10% of the population already suffers from diabetes mellitus with a tendency to rise even further. For a minor proportion of the patients concerned pancreas transplantation forms a probate therapeutic procedure to restore normoglycemia mostly performed for diabetics with terminal renal failure as a simultaneous pancreas and kidney transplantation (SPK). Thus the patient is not only liberated from dialysis but the recurrence of diabetic nephropathy in the simultaneously transplanted kidney is prevented and diabetic late syndrome can be postponed or partly ameliorated. Initially performed using the duct occlusion technique, in later years with the bladder drainage technique, the standard procedure is currently enteral drainage. Systemic as well as portal venous drainage are equally appropriate procedures. Outcomes have now reached above 80% for 1-year insulin independence and around 70% for 5-year insulin independence, as well as more than 90% for 5-year kidney and patient survival; thus SPK transplantation has advanced to a life-saving procedure. The decline in transplant numbers, however, is due to improved nephrological therapy in diabetics as well as to the increasing marginality of donor organs.     

门静脉回流的胰肾联合移植大鼠模型制备

目的探索建立大鼠胰肾联合移植（SPK）模型的手术技巧。方法以雄性健康近交封闭群SD大鼠作为供体，Wistar大鼠作为受体，行整块胰肾十二指肠移植。采用供体腹主动脉和受体腹主动脉端侧吻合，供体门静脉和受体肠系膜上静脉端侧吻合，供体肾静脉和受体肾静脉袖套式吻合，供体输尿管膀胱瓣与受体膀胱吻合，最后将十二指肠近端结扎，远端腹壁造瘘。结果共正式实验40例，手术成功率为85％。供体肾、胰植入受体后立即恢复良好的血液循环，移植后24h血糖、肌酐降为正常，术后移植胰腺具有内分泌功能。结论此模型切实可行，手术成功率高，术后并发症少，可用于SPK基础方面的研究。     

Simultaneous pancreas and kidney transplantation: a feasible procedure in selected patients.

We analyzed the overall results of 24 simultaneous pancreas and kidney transplantations (SPK), performed in our hospital between April 1986 and June 1990. All patients had type I diabetes mellitus and end-stage renal failure. We used bladder drainage of the pancreatic exocrine secretions through a duodenocystostomy. The blood vessels of both grafts were anastomosed to the iliac vessels. The immunosuppressive management was triple-therapy with cyclosporin, azathioprine and prednisone. All organs were transplanted without matching donors and recipients for HLA. At the time of transplantation, mean recipient age was 37 yr; the average duration of diabetes was 22 yr. After disappointing results in the first 4 patients, the pancreas was placed intraperitoneally instead of extraperitoneally and the antibiotic drug regimen was altered. In the second group (n = 20), patient survival was 100%; 1-yr pancreas and kidney graft survival were 65 and 62%, respectively. Duration of hospitalization and pancreas and kidney graft loss were positively correlated with the number of rejection episodes. After 1 yr of follow-up, the mean creatinine clearance was 62 ml/min and the mean HbA1c was 5.5%. Blood glucose levels and oral glucose tolerance tests were also normal. We conclude that patient and graft survival after SPK are satisfactory, although rejection-related morbidity is still a major problem.     

Pancreatic transplantation: The cambridge experience

In contrast to heterotopic pancreas transplantation and conventional insulin therapy the paratopic positioning of a segmental pancreas graft provides physiological endocrine hormone delivery into the portal venous circulation. Metabolic studies performed on previously insulin dependent diabetic patients with renal failure with functioning paratopic pancreas transplants and heterotopic kidney grafts from the same donor showed near normal day to day glucose control with normal fasting glucose levels and normal HbA₁ values. Hyperinsulinaemia was not seen in these patients. The effect of denervation of the pancreatic graft on the entero-insular axis and its influence on the islets were investigated. The incretin effect was preserved indicating a significant hormonal stimulation of the enteroinsular axis.     

Simultaneous islet–kidney vs pancreas–kidney transplantation in type 1 diabetes mellitus: a 5 year single centre follow-up

Aims/hypothesis The aim of this study was to compare the long-term outcomes—in terms of glucose control, renal function and procedure-related complications—of simultaneous islet–kidney (SIK) transplantation with those of simultaneous pancreas–kidney (SPK) transplantation in patients with type 1 diabetes mellitus. Methods HbA_1c, need for insulin, GFR and complication rate were compared between 13 recipients of SIK and 25 recipients of SPK transplants at the same institution. The mean follow-up was 41 months. Results Two primary organ non-functions occurred in the SIK group. HbA_1c did not differ at any time point during follow-up in the SIK group compared with the SPK group (mean during follow-up 6.3 vs 5.9%). Similarly, kidney function over time was not different between the two groups. A higher rate of insulin independence following SPK transplantation (after 1 year 96 vs 31% in the SIK group) was counterbalanced by a higher rate of serious adverse events (40% relaparotomies vs 0% in the SIK group). Conclusions/interpretation The endogenous insulin production achieved by islet transplantation, combined with optimal insulin therapy, was sufficient for maintaining near-normal glucose levels. In terms of glucose control, islet transplantation provides results comparable to those achieved with pancreas transplantation. However, SPK results in a higher rate of insulin independence, albeit at the cost of more surgical complications. These results have led to a new paradigm in islet transplantation at our institution, where the primary goal is not insulin independence, but good glucose control and avoidance of severe hypoglycaemia.     

Diversion of the gastroduodenal vein: an in situ model of systemic insulin drainage

A technique of diversion of the gastroduodenal vein in a canine model is described to compare long-term metabolic effects of systemic versus portal pancreatic endocrine drainage. The vein was transected at its entrance into the portal vein and either diverted to the inferior vena cava (systemic group) or reanastomosed to the portal vein (portal group). All remaining venous drainage of the pancreas was interrupted. An additional group of animals underwent laparotomy without manipulation of pancreatic vasculature (sham group). Fasting peripheral insulin and glucose values were determined 3 months postoperatively. Fasting insulin values were significantly higher in the systemic group (mean 10.7 +/- 1.06 U/ml) than in the portal (5.8 +/- 0.70, P = 0.002) and sham (6.4 +/- 0.68, P = 0.01) groups. Fasting glucose values were not significantly different in the three groups. At sacrifice, venous thrombosis was noted in one systemically diverted dog (6.7%). All other anastomoses were patent. No significant collateralization was apparent in any group. No significant complications were noted. This procedure simulates the hormonal milieu created by heterotopic pancreatic transplantation while preserving pancreatic innervation and exocrine function, and serves as an excellent model for investigating the effects of systemic hyperinsulinemia on protein, carbohydrate, and lipid metabolism.     

A comparison of portal venous versus systemic venous drainage in pancreas transplantation

Background

The decision to utilize portal or systemic venous drainage in pancreas transplantation is surgeon- and center-dependent. Information regarding the superior method is based on single-center reports and animal models.

Effects of chronic systemic insulin delivery on insulin action in dogs

Summary The metabolic consequences of the prolonged systemic insulin delivery associated with human pancreas transplantation have not been precisely defined. To determine if systemic insulin delivery in the absence of immunosuppressive agents results in alterations in hepatic or extrahepatic insulin action, three groups of dogs were studied 2 months after either a sham operation or after their pancreatic venous drainage was severed and anastomosed to the inferior vena cava or portal vein (sham, peripheral and portal groups, respectively). The pattern of venous drainage was documented by measuring vena cava and portal insulin concentrations before and after glucose injection. Systemic insulin concentrations were higher (p<0.05) in the peripheral group than in the portal group both following a 14-h fast and after intravenous glucose. During a hyperinsulinaemic euglycaemic clamp (1 mU·kg^–1·min^–1), glucose utilization (measured using [6³H] glucose) was slightly lower (p=0.07) in the peripheral than in the portal group. Hepatic glucose release was equal in all groups. Carbon dioxide incorporation into glucose (an estimate of gluconeogenesis) was higher in the portal than peripheral group in the fasted state but not during insulin infusion. Plasma concentrations and flux rates of fatty acids and amino acids did not differ between groups. We conclude that chronic systemic insulin delivery results in a) systemic but not portal hyperinsulinaemia, b) a minimal impairment in insulin-stimulated glucose uptake, without altering insulin-induced suppression of hepatic glucose release, and c) no effect on fatty acid or amino acid turnover. Although chronic systemic insulin delivery appears to have a minimal effect on insulin action, it remains to be determined whether it has other deleterious effects such as enhancing atherogenesis.     

Changes of inducible protein-10 and regulated upon activation, normal T cell expressed and secreted protein in acute rejection of pancreas transplantation in rats

AIM: To investigate the role of IFN-γinducible protein -10 (IP-10) and regulated upon activation, normal T cell expressed and secreted (RANTES) protein in acute pancreatic allograft rejection in rats. METHODS: An experimental pancreas transplantation model was established using diabetic SD rats as the recipient, induced by applying streptozocin (STZ). Pancreas transplantation was performed with a physiologic method of portal venous and enteric drainage. Rats were divided into two groups, isograft group (group A, n = 24) and allograft group (group B, n = 24) in which either healthy SD rats or Wistar rats served as donors, respectively. Twelve diabetic or healthy SD rats were used as controls. At d 1, 4, 7, and 10 post transplantation, serum IP-10 and RANTES were assessed by ELISA and their expression in the allografts was determined by immunohistochemistry. RESULTS: In group B (allograft group), the development of acute rejection was significantly correlated with increased serum concentration and tissue expression of IP-10 and RANTES, with a peak level at d 7 post transplantation. In contrast, there was no obvious change before and after transplantation in group A (isograft group). CONCLUSION: Our study suggests a possible role of IP-10 and RANTES in acute rejection and early monitoring of chemokines may be helpful in predicting the outcome of pancreas transplantation.